1. Field of the Invention
The present invention relates generally to targeting nucleic acid molecules and mitochondrial diseases and disorders.
2. Description of the Related Art
RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome and mutations in the human mitochondrial genome are implicated in a plethora of human conditions, such as neurodegenerative and cardiovascular diseases, muscular disorders, and the process of aging. See e.g. Wallace (1994) PNAS USA 91: 8739-8746; and Kyriakouli et al. (2008) Gene Ther 15: 1017-1023. Unfortunately, RNA import pathways and factors that control RNA import are poorly understood. In addition, the in vivo rescue of function in mitochondria with mt-tRNA mutations has proven challenging (Alfonzo & Soll (2009) Biol Chem 390: 717-722). Thus, prior art methods of rescuing mitochondrial function due to defects in mitochondrial genomes have been restricted to correcting the defects by using foreign protein factors or large multi-subunit aggregates to introduce non-native tRNAs into cells, and these methods have low efficiency and poor reproducibility in disease-relevant settings. See e.g. Kolesnikova et al. (2004) Hum Mol Genet 13: 2519-2534; Mahata et al. (2006) Science 314: 471-474; and Kolesnikova et al. (2000) Science 289: 1931-1933.
Consequently, a need exists for methods and compositions for treating deleterious mitochondrial DNA (mtDNA) alterations.